Abstract
BackgroundChagas disease is the third most important neglected tropical disease. There is no vaccine available, and only two drugs are generally prescribed for the treatment, both of which with a wide range of side effects. Our study of T. cruzi PHBs revealed a pleiotropic function in different stages of the parasite, participating actively in the transformation of the non-infective replicative epimastigote form into metacyclic trypomastigotes and also in the multiplication of intracellular amastigotes.Methodology/principal findingsTo obtain and confirm our results, we applied several tools and techniques such as electron microscopy, immuno-electron microscopy, bioinformatics analysis and molecular biology. We transfected T. cruzi clones with the PHB genes, in order to overexpress the proteins and performed a CRISPR/Cas9 disruption to obtain partially silenced PHB1 parasites or completely silenced PHB2 parasites. The function of these proteins was also studied in the biology of the parasite, specifically in the transformation rate from non-infective forms to the metacyclic infective forms, and in their capacity of intracellular multiplication.Conclusion/significanceThis research expands our understanding of the functions of PHBs in the life cycle of the parasite. It also highlights the protective role of prohibitins against ROS and reveals that the absence of PHB2 has a lethal effect on the parasite, a fact that could support the consideration of this protein as a possible target for therapeutic action.
Highlights
Trypanosoma cruzi, a flagellate protozoan parasite that belongs to the order Kinetoplastida, is the etiologic agent of Chagas disease, a neglected tropical disease [1,2] endemic in 21 Latin American countries and distributed from the south of the USA to Argentina and Chile [3]
Trypanosoma cruzi is the etiological agent of American trypanosomiasis or Chagas disease
We describe for the first time the function and location of Trypanosoma cruzi proteins Prohibitin 1 and 2
Summary
Trypanosoma cruzi, a flagellate protozoan parasite that belongs to the order Kinetoplastida, is the etiologic agent of Chagas disease, a neglected tropical disease [1,2] endemic in 21 Latin American countries and distributed from the south of the USA to Argentina and Chile [3]. After 8–15 days, the E form is transformed into non-proliferative metacyclic trypomastigotes (M) in the terminal intestine and rectum of the insect. This M stage is excreted in the insect’s dejections, together with the feces and urine. When the metacyclic trypomastigotes infect mammalian host cells, they transform into the intracellular amastigote stage (A), a form that multiplies and occupies the cytoplasm of the host cell and, after several rounds of multiplication, differentiates into the non-multiplicative but infective trypomastigote. Our study of T. cruzi PHBs revealed a pleiotropic function in different stages of the parasite, participating actively in the transformation of the non-infective replicative epimastigote form into metacyclic trypomastigotes and in the multiplication of intracellular amastigotes
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